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Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents

International Journal of Obesity volume 29, pages 362–368 (2005)Cite this article

Abstract

BACKGROUND:

There are conflicting results for ghrelin changes in reduction of overweight. Increasing ghrelin levels in weight reduction are considered to be responsible for compensatory mechanisms that make the reduction of overweight unlikely to be sustained.

METHODS:

We have analyzed fasting serum ghrelin levels, weighed dietary record and, as biochemical markers of clinically relevant reduction of overweight, leptin, adiponectin and insulin levels and insulin resistance measured by homeostasis model assessment (HOMA) at baseline and after a 1-y outpatient weight reduction program based on a high-carbohydrate and low-fat diet in 37 obese children (median age 10 y). We divided these children into two subgroups according to their degree of weight loss (substantial reduction of overweight: decrease in SDS-BMI≥0.5). Furthermore, we analyzed ghrelin levels in 16 normal-weight children.

RESULTS:

Obese children demonstrated significant (P<0.001) lower ghrelin levels compared to normal-weight children. Daily caloric intake (P=0.004) and percentage fat content decreased significantly (P<0.001), while percentage carbohydrate content increased significantly (P=0.003) between baseline and 1-y follow-up in the obese children. The substantial reduction of overweight in 16 children (median SDS-BMI=−0.7) was associated with significant changes in insulin resistance (median decrease of HOMA 27%; P=0.013), insulin (median decrease 25%, P=0.036), adiponectin (median increase 15%; P=0.003), and leptin levels (median decrease 19%; P=0.023), while there were no significant changes in ghrelin levels (median increase 4%; P=0.326). In the 21 children without substantial reduction of overweight (median SDS-BMI=−0.3), there were no significant changes in insulin resistance and in insulin, adiponectin, leptin and ghrelin levels.

CONCLUSIONS:

We conclude that in obese children, low-fat high-carbohydrate diet-induced weight loss does not change ghrelin secretion, but significantly decreases leptin levels, increases adiponectin levels and improves insulin resistance determined by significantly decreased insulin resistance indices as well as lowered serum insulin levels.

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References

  1. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S . Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002; 87: 240–244.

    Article  CAS  Google Scholar 

  2. Horvath TL, Diano S, Sotonyi P, Heimau M, Tschop M . Minireview: ghrelin and the regulation of energy balance—a hypothalamic perspective. Endocrinology 2001; 142: 4163–4169.

    Article  CAS  Google Scholar 

  3. Lee HM, Wang G, Englander EW, Kojima M, Greeley GH . Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 2002; 143: 185–190.

    Article  CAS  Google Scholar 

  4. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K . Ghrelin is a growth-hormone-releasing acylated peptide from the stomach. Nature 1999; 402: 656–660.

    Article  CAS  Google Scholar 

  5. Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino MA, Kasuga M . Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 2001; 120: 337–345.

    Article  CAS  Google Scholar 

  6. Tschöp M, Smiley DL, Heiman ML . Ghrelin induces adiposity in rodents. Nature 2000; 407: 908–913.

    Article  Google Scholar 

  7. Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, Müller J, Skakkebaek NE, Heiman ML, Birkett M, Attanasio AM, Kiess W, Rascher W . Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab 1997; 82: 2904–2910.

    CAS  Google Scholar 

  8. Campfield LA, Smith FJ, Burn P . The OB protein (leptin) pathway—a link between adipose tissue mass and central neural networks. Horm Metab Res 1996; 28: 619–632.

    Article  CAS  Google Scholar 

  9. De Ambrogi M, Volpe S, Tamanini C . Ghrelin central and peripheral effects of a novel peptydil hormon. Med Sci Monit 2003; 9: 217–224.

    Google Scholar 

  10. Bellone S, Rapa A, Vivenza D, Castellino N, Petri A, Bellone J, Me E, Broglio F, Prodam F, Ghigo E, Bona G . Circulating ghrelin levels as function of gender, pubertal status and adiposity in childhood. J Endocrinol Invest 2002; 25: 13–15.

    Article  Google Scholar 

  11. Tschöp M, Weyer C, Tataranni A, Devanarayan V, Ravussin E, Heiman ML . Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707–709.

    Article  Google Scholar 

  12. Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K . Plasma acylation-stimulation protein, adiponectin, leptin, and ghrelin before and after reduction of overweight induced by gastric surgery in morbidly obese subjects. J Clin Endocrinol Metab 2003; 88: 1594–1602.

    Article  CAS  Google Scholar 

  13. Hansen TK, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen JS, Jorgensen JO . Reduction of overweight increases circulating levels of ghrelin in human obesity. Clin Endocrinol 2002; 56: 203–206.

    Article  CAS  Google Scholar 

  14. Soriano-Guillen L, Barrios V, Campos-Barros A, Argente J . Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation. J Pediatr 2004; 144: 36–42.

    Article  CAS  Google Scholar 

  15. Hanusch-Enserer U, Cauza E, Brabant G, Dunky A, Rosen H, Pacini G, Tuchler H, Prager R, Roden M . Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding. J Clin Endocrinol Metab 2004; 87: 3352–3358.

    Article  Google Scholar 

  16. Ravussin E, Tschop M, Morales S, Bouchard C, Heiman ML . Plasma ghrelin concentration and energy balance: overfeeding and negative energy balance studies in twins. J Clin Endocrinol Metab 2001; 86: 4547–4551.

    Article  CAS  Google Scholar 

  17. Weigle DS, Cummings DE, Newby PD, Breen PA, Frayo RS, Matthys CC, Callahan HS, Purnell J . Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet. J Clin Endocrinol Metab 2003; 88: 1577–1586.

    Article  CAS  Google Scholar 

  18. Morinigo R, Casamitjana R, Moize V, Lacy AM, Delgado S, Gomis R, Vidal J . Short-term effects of gastric bypass surgery on circulating ghrelin levels. Obes Res 2004; 12: 1108–1116.

    Article  Google Scholar 

  19. Doucet E, Pomerleau M, Harper ME . Fasting and postprandial total ghrelin remain unchanged after short-term energy restriction. J Clin Endocrinol Metab 2004; 89: 1727–1732.

    Article  CAS  Google Scholar 

  20. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ . Plasma ghrelin levels after diet-induced reduction of overweight or gastric bypass surgery. N Engl J Med 2002; 346: 1623–1630.

    Article  Google Scholar 

  21. Kromeyer-Hauschild K, Wabitsch M, Geller F, Ziegler A, Geiß HC, Hesse V, Hippel V, Jaeger U, Johnsen D, Müller G, Korte W, Kunze D, Menner K, Müller M, Niemann-Pilatus A, Remer Th, Schaefer F, Wittchen HU, Zabransky S, Zellner K, Hebebrand J . Percentiles of body mass index in children and adolescents evaluated from different regional German studies. Monatsschr Kinderheilkd 2001; 149: 807–818.

    Article  Google Scholar 

  22. Reinehr T, Kersting M, Alexy U, Andler W . Long-term follow-up of overweight children: after training, after a single consultation session and without treatment. J Pediatr Gastroenterol Nutr 2003; 37: 72–74.

    Article  Google Scholar 

  23. Reinehr T, Brylak K, Alexy U, Kersting M, Andler W . Predictors to success in outpatient training in obese children and adolescents. Int J Obes Relat Metab Disord 2003; 27: 1087–1092.

    Article  CAS  Google Scholar 

  24. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  25. Cole TJ . The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990; 44: 45–60.

    CAS  PubMed  Google Scholar 

  26. Kersting M, Sichert-Hellert W, Lausen B, Alexy U, Manz F, Schöch G . Energy intake of 1 to 18 year old German children and adolescents. Z Ernährungswiss 1998; 37: 47–55.

    Article  CAS  Google Scholar 

  27. Reinehr T, Andler W . Changes in the atherogenic risk-factor profile according to degree of reduction of overweight. Arch Dis Child 2004; 89: 419–422.

    Article  CAS  Google Scholar 

  28. Reinehr T, Kiess K, Kapellen T, Andler W . Insulin sensitivity among obese children and adolescents, according to degree of weight loss. Pediatrics 2004; 114: 1–5.

    Article  Google Scholar 

  29. Reinehr T, Roth C, Menke T, Andler W . Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab 2004; 89: 3790–3794.

    Article  CAS  Google Scholar 

  30. Monteleone P, Bencivenga R, Longobardi N, Serritella C, Maj M . Differential responses of circulating ghrelin to high-fat or high-carbohydrate meal in healthy women. J Clin Endocrinol Metab 2003; 88: 5510–5514.

    Article  CAS  Google Scholar 

  31. Erdmann J, Topsch R, Lippl F, Gussmann P, Schusdziarra V . Postprandial response of plasma ghrelin levels to various test meals in relation to food intake, plasma insulin, and glucose. J Clin Endocrinol Metab 2004; 89: 3048–3054.

    Article  CAS  Google Scholar 

  32. Ahima RS, Flier JS . Leptin. Annu Rev Physiol 2000; 125: 285–297.

    Google Scholar 

  33. Arvat E, Di Vito L, Broglio F, Papotti M, Muccioli G, Dieguez C, Casanueva FF, Deghenghi R, Camanni F, Ghigo E . Preliminary evidence that Ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. J Endocrinol Invest 2000; 23: 493–495.

    Article  CAS  Google Scholar 

  34. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, McNamara JR, Schaefer MM, Rasmussen H, Ordovas JM . Body weight and low-density lipoprotein cholesterol after consumption of a low-fat ad libitum diet. JAMA 1995; 274: 1450–1455.

    Article  CAS  Google Scholar 

  35. Siggaard R, Raben A, Astrup A . Weight loss during 12 weeks’ ad libitum carbohydrate-rich diet in overweight and normal-weight subjects at a Danish work site. Obes Res 1996; 4: 347–356.

    Article  CAS  Google Scholar 

  36. Astrup A, Grunwald GK, Melanson EL, Saris WH, Hill JO . The role of low-fat diets in body weight control: a meta-analysis of ad libitum dietary intervention studies. Int J Obes Relat Metab Disord 2000; 24: 1545–1552.

    Article  CAS  Google Scholar 

  37. Ikezaki A, Hosoda H, Ito K, Iwama S, Miura N, Matsuoka H, Kondo C, Kojima M, Kangawa K, Sugihara S . Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin in obese children and adolescents. Diabetes 2002; 51: 3408–3411.

    Article  CAS  Google Scholar 

  38. Haqq AM, Farroqi IS, Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, LaFranchi SH, Purnell JQ . Serum ghrelin levels are inversely correlated with body mass index, age and insulin concentrations in normal children and are markedly increased in Prader–Willi syndrome. J Clin Endocrinol Metab 2003; 88: 174–178.

    Article  CAS  Google Scholar 

  39. Whatmore AJ, Hall CM, Jones J, Westwood M, Clayton PE . Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol (Oxf) 2003; 59: 649–654.

    Article  CAS  Google Scholar 

  40. Purnell JQ, Weigle DS, Breen P, Cummings DE . Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 2003; 88: 5747–5752.

    Article  CAS  Google Scholar 

  41. Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein HH, Tschop M, Klein J . Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res 2002; 34: 640–645.

    Article  CAS  Google Scholar 

  42. Erdmann J, Lippl F, Schusdziarra V . Differential effect of protein and fat on plasma ghrelin levels in man. Regul Pept 2003; 116: 101–107.

    Article  CAS  Google Scholar 

  43. Wallace TM, Matthews DR . The assessment of insulin resistance in man. Diabet Med 2002; 19: 527–534.

    Article  CAS  Google Scholar 

  44. Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA . Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care 2002; 25: 2081–2087.

    Article  CAS  Google Scholar 

  45. McGowan MJ, Harrington KE, Kiely M, Robson PJ, Livingstone MB, Gibney MJ . An evaluation of energy intakes and the ratio of energy intake to estimated basal metabolic rate (EI/BMRest) in the North/South Ireland Food Consumption Survey. Public Health Nutr 2001; 4: 1043–1050.

    Article  CAS  Google Scholar 

  46. Ariyasu H, Takaya K, Hosoda H, Iwakura H, Ebihara K, Mori K, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K . Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the action of ghrelin. Endocrinology 2002; 143: 3341–3350.

    Article  CAS  Google Scholar 

  47. Stock S, Pinzon J, Wong ACK, Leichner P, Chanoine JP . Changes in ghrelin and hunger following a mixed meal in anorexic, obese and control female adolescents (abstract). Horm Res 2003; 60 (Suppl 2): 131.

    Google Scholar 

  48. Casanueva FF, Dieguez C . Ghrelin, the link connecting growth with metabolism and energy homeostasis. Rev Endocr Metab Disord 2002; 3: 325–338.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank R Maslak, Children's Hospital University of Bonn, for outstanding laboratory contributions to this work.

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Authors and Affiliations

  1. Vestische Kinder- und Jugendklinik Datteln, University of Witten-Herdecke, Germany

    T Reinehr & W Andler

  2. Division of Neuroscience, Oregon Health & Science University West Campus, USA

    C L Roth

  3. Children's Hospital University of Bonn, Germany

    C L Roth

  4. Research Institute of Child Nutrition Dortmund, Germany

    U Alexy & M Kersting

  5. Hospital for children and adolescents, University of Leipzig, Germany

    W Kiess

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Correspondence to T Reinehr.

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Reinehr, T., Roth, C., Alexy, U. et al. Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents. Int J Obes 29, 362–368 (2005). https://doi.org/10.1038/sj.ijo.0802913

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